Applications

The application notes include recommended starting dilutions; optimal dilutions/concentrations should be determined by the end user.

Application

Abreviews

Notes

WB

Use a concentration of 1 - 2 µg/ml. Detects a band of approximately 265 kDa (predicted molecular weight: 289 kDa).Can be blocked with KAT3B / p300 peptide (ab4914).

IP

Use at an assay dependent concentration.

Target

FunctionFunctions as histone acetyltransferase and regulates transcription via chromatin remodeling. Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation. Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. Also functions as acetyltransferase for nonhistone targets. Acetylates 'Lys-131' of ALX1 and acts as its coactivator in the presence of CREBBP. Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function. Acetylates HDAC1 leading to its inactivation and modulation of transcription. Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2. Plays a role as a coactivator of NEUROD1-dependent transcription of the secretin and p21 genes and controls terminal differentiation of cells in the intestinal epithelium. Promotes cardiac myocyte enlargement. Can also mediate transcriptional repression. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. Acetylates FOXO1 and enhances its transcriptional activity.

Involvement in diseaseNote=Defects in EP300 may play a role in epithelial cancer.Note=Chromosomal aberrations involving EP300 may be a cause of acute myeloid leukemias. Translocation t(8;22)(p11;q13) with KAT6A.Rubinstein-Taybi syndrome 2 (RSTS2) [MIM:613684]: A disorder characterized by craniofacial abnormalities, postnatal growth deficiency, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies. Some individuals with RSTS2 have less severe mental impairment, more severe microcephaly, and a greater degree of changes in facial bone structure than RSTS1 patients. Note=The disease is caused by mutations affecting the gene represented in this entry.

DomainThe CRD1 domain (cell cycle regulatory domain 1) mediates transcriptional repression of a subset of p300 responsive genes; it can be de-repressed by CDKN1A/p21WAF1 at least at some promoters. It conatins sumoylation and acetylation sites and the same lysine residues may be targeted for the respective modifications. It is proposed that deacetylation by SIRT1 allows sumoylation leading to suppressed activity.

Post-translationalmodificationsAcetylated on Lys at up to 17 positions by intermolecular autocatalysis. Deacetylated in the transcriptional repression domain (CRD1) by SIRT1, preferentially at Lys-1020.Citrullinated at Arg-2142 by PADI4, which impairs methylation by CARM1 and promotes interaction with NCOA2/GRIP1.Methylated at Arg-580 and Arg-604 in the KIX domain by CARM1, which blocks association with CREB, inhibits CREB signaling and activates apoptotic response. Also methylated at Arg-2142 by CARM1, which impairs interaction with NCOA2/GRIP1.Sumoylated; sumoylation in the transcriptional repression domain (CRD1) mediates transcriptional repression. Desumoylated by SENP3 through the removal of SUMO2 and SUMO3.Probable target of ubiquitination by FBXO3, leading to rapid proteasome-dependent degradation.Phosphorylated by HIPK2 in a RUNX1-dependent manner. This phosphorylation that activates EP300 happens when RUNX1 is associated with DNA and CBFB. Phosphorylated by ROCK2 and this enhances its activity. Phosphorylation at Ser-89 by AMPK reduces interaction with nuclear receptors, such as PPARG.

Cellular localizationCytoplasm. Nucleus. In the presence of ALX1 relocalizes from the cytoplasm to the nucleus. Co-localizes with ROCK2 in the nucleus.

Thank you for contacting us. As I mentioned, none of our p300 antibodies have been tested for cross-reactivity with CREB. The epitope that ab37142 binds has been mapped to a region between and including amino acids 1921 to 2023 of the human p300 protei...